Gene regulation of intracellular adhesion molecule-1 (ICAM-1): A molecule with multiple functions.

Intracellular adhesion molecule 1 (ICAM-1) is one of the most extensively studied inducible cell adhesion molecules which is responsible for several immune functions like T cell activation, extravasation, inflammation, etc. The molecule is constitutively expressed over the cell surface and is regulated up / down in response to inflammatory mediators like cellular stress, proinflammatory cytokines, viral infection. These stimuli modulate the expression of ICAM-1 primarily through regulating the ICAM-1 gene transcription. On account of the presence of various binding sites for NF-κB, AP-1, SP-1, and many other transcription factors, the architecture of the ICAM-1 promoter become complex. Transcription factors in union with other transcription factors, coactivators, and suppressors promote their assembly in a stereospecific manner on ICAM-1 promoter which mediates ICAM-1 regulation in response to different stimuli. Along with transcriptional regulation, epigenetic modifications also play a pivotal role in controlling ICAM-1 expression on different cell types. In this review, we summarize the regulation of ICAM-1 expression both at the transcriptional as well as post-transcriptional level with an emphasis on transcription factors and signaling pathways involved.

COVID-19 lockdown: a boon in boosting the air quality of major Indian Metropolitan Cities.

ABSTRACT: The COVID-19 lockdown has not only helped in combating the community transmission of SARS-CoV-2 but also improved air quality in a very emphatic manner in most of the countries. In India, the first phase of COVID-19 lockdown came into force on March 25, 2020, which was later continued in the next phases. The purpose of this study was to investigate the result of lockdown on air quality of major metropolitan cities-Delhi, Mumbai, Kolkata, Chennai, Bengaluru, Hyderabad, Jaipur, and Lucknow-from March 25 to May 3, 2020. For this study, the concentration of six criteria air pollutants (PM2.5, PM10, CO, NO2, SO2, and O3) and air quality index during the COVID-19 lockdown period was compared with the same period of the previous year 2019. The results indicate a substantial improvement in air quality with a drastic decrease in the concentration of PM2.5, PM10, CO, and NO2, while there is a moderate reduction in SO2 and O3 concentration. During the lockdown period, the maximum reduction in the concentration of PM2.5, PM10, CO, NO2, SO2, and O3 was observed to be - 49% (Lucknow), - 57% (Delhi), - 75% (Mumbai), - 68% (Kolkata), - 48% (Mumbai), and - 29% (Hyderabad), respectively. The value of the air quality index (AQI) also dwindled significantly during the COVID-19 lockdown period. The maximum decline in AQI was observed - 52% in Bengaluru and Lucknow. The order of AQI was satisfactory > moderate > good > poor and the frequency order of prominent pollutants was O3 > PM10 > PM2.5 > CO > NO2 > SO2 during the lockdown period in all the aforementioned metropolitan cities.

Mechanistic basis of co-stimulatory CD40-CD40L ligation mediated regulation of immune responses in cancer and autoimmune disorders.

Generation of an accurate humoral and a cell mediated adaptive immune responsesare dictated by binding of an antigen to a T- and a B-cell receptor, respectively (first signal) followed by ligation of costimulatory molecules (second signal). CD40, a costimulatory receptor molecule, expressed mainly on antigen presenting cells, some non-immune cells and tumors, binds to CD40 ligand molecule expressed transiently on T-cells and non-immune cells under inflammatory conditions. In the past decade, the CD40-CD40L interaction has emerged as an immune-potentiating system that governs and regulates host immune response against various diseases and pathogens, failing of which results in detrimental patho-physiologies including cancer and autoimmune disorders. CD40-CD40L transduces immune signals intracellularly via TRAF-dependent and independent mechanisms and further downstream by different MAPK pathways and transcription factors such as NF-κB, p38 etc. While CD40 signaling pathway through its cognate interaction between B and T cells promotes activation and proliferation of B-cells, Ig class switching, and generation of B cell memory; however, CD40-CD40L interaction involving other APCs and non-immune cells relay distinct cell signaling resulting in production of a variety of cytokines/chemokines and cell adhesion molecules ultimately conferring host defense against pathogen. In cancer and autoimmune disorders, CD40-CD40L interaction is also responsible for aberrant expression of many disease specific markers, class I/II MHC molecules and other co-stimulatory molecules such as B7 and CD28 in cell- and disease-specific manner. In the present review, the current state of understanding about the CD40-CD40L mediated regulation of immune and non-immune cells is presented. The current paradigm is to target CD40 using agonist anti-CD40 mAbs alone or in synergistic combination with chemotherapy in order to harness or confer anti-tumor and anti-inflammatory immunity.

Effect of treatment of cow's urine "Gomutra" and antioxidants in alleviating the lindane-induced oxidative stress in kidney of Swiss mice (Mus musculus).

The study aimed to evaluate the effect of cow urine and combination of antioxidants against lindane induced oxidative stress in Swiss mice. Male healthy mice, 8-10 weeks old, weighing 30 ± 5 g were randomly selected and divided into eight groups, namely, control (C); lindane (L); antioxidant (A), antioxidant+lindane (A+L), cow urine (U), cow urine+lindane (U+L), cow urine+antioxidants (U+A) and cow urine+antioxidants+lindane (U+A+L). Group C animals were administered only the vehicle (olive oil); doses selected for other treatments were: lindane: 40 mg/kg b.w.; antioxidants: 125 mg/kg b.w. (vitamin C: 50 mg/kg b.w., vitamin E: 50 mg/kg b.w., α-lipoic acid: 25 mg/kg b.w.) and cow urine: 0.25 ml/kg b.w. In group A+L and U+L antioxidants and cow urine were administered 1 h prior to lindane administration and in group U+A and U+A+L cow urine was administered 10 min before antioxidants. All treatments were administered orally continuously for 60 days. Lindane treated group showed increased lipid peroxidation, whereas glutathione, glutathione peroxidase, superoxide dismutase, catalase, protein and endogenous levels of vitamin C and E were significantly decreased compared to control. Administration of cow urine and antioxidants alleviated the levels of these biochemical parameters.

Modulation of acid phosphatase and lactic dehydrogenase in hexachlorocyclohexane-induced hepatocarcinogenesis in mice.

The present study was designed to elucidate the involvement of acid phosphatase (ACP) in metastasis and lactate dehydrogenase (LDH) as an immediate compensatory alleviation mechanism for energy stress in liver lesions induced by hexachlorocyclohexane in Swiss mice. Animals were continuously exposed to hexachlorocyclohexane (500 ppm) for 2, 4, and 6 months. Neoplastic nodules and tumors developed after continuous exposure for 4 and 6 months, respectively. The distribution pattern of both enzymes markedly varied in neoplastic nodules and tumors. Intense ACP activity was more observed only in sinusoids and blood vessels of neoplastic nodule, whereas an overall increase in ACP activity was observed in the tumor. Noticeably, a significant decline in LDH activity was noted after 2 and 4 months of exposure, whereas LDH in a tumor region showed intense enzymatic activity. The role of acid phosphate in metastasis and LDH in oxidative stress during hepatocarcinogenesis induced by hexachlorocyclohexane has been discussed.

Alleviation of lindane induced toxicity in testis of Swiss mice (Mus musculus) by combined treatment with vitamin C, vitamin E and alpha-lipoic acid.

Mitigation of lindane induced toxicity in testis of Swiss mice by combined treatment with vitamin C, vitamin E and alpha-lipoic acid has been evaluated. Male healthy mice (40), 8-10 weeks old were randomly selected and divided into 4 groups, control (C); lindane (L); antioxidant (A) and antioxidant plus lindane (A+L). Group C animals were administered only the vehicle (olive oil); in group L lindane was administered orally at a dose of 40 mg/kg body wt.; in group A combination of antioxidants at a dose of 125 mg/kg body wt.(vitamin C: 50 mg/kg body wt., vitamin E: 50 mg/kg body wt. and alpha-lipoic acid: 25 mg/kg body wt.) was administered orally; in group A+L both antioxidants (125 mg/kg body wt.) and lindane (40 mg/kg body wt.) were administered at their respective doses. In group A+L antioxidants were administered 1 h prior to lindane administration. All treatments were continuously given for 60 days. Histopathological changes due to lindane intoxication indicated shrunken and distorted seminiferous tubules, sparse Leydig cells and blood vessels and atrophy in the tissue. The testis weight also decreased significantly. Lindane treated group showed increased lipid peroxidation, whereas glutathione, glutathione peroxidase, superoxide dismutase, catalase and protein were significantly decreased compared to control. Lindane induced damage was minimized by administration of antioxidants. Results suggest that combined pretreatment with antioxidants can alleviate the damage caused to testis by lindane.